Alpha, beta-unsaturated sulfoxides for treating proliferative disorders

Abstract

αβ-Unsaturated sulfoxides of Formula I: are useful as antiproliferative agents including, for example, anticancer agents, and as radioprotective and chemoprotective agents.

1. A compound of Formula IA: 
       
         
           
           
               
               
           
         
       
       wherein:
 A 1  is aryl or heteroaryl and x is 0, 1, 2, 3, 4 or 5; 
 either B 1  is aryl and y is 1, 2, 3, 4 or 5, or B 1  is heteroaryl and y is 0, 1, 2, 3, 4 or 5; 
 provided that x does not exceed the number of substitutable positions of the ring to which each R a  is attached; and y does not exceed number of substitutable positions of the ring to which each R b  is attached; 
 n is 1; 
 R 1  is —H, —(C 1 -C 8 )hydrocarbyl, —CN, —CO 2 (C 1 -C 6 )alkyl or halo(C 1 -C 6 )alkyl; 
 the configuration of the substituents on the carbon-carbon double bond is either E- or Z—; 
 the configuration of the substituents on the sulfoxide sulfur atom is R—, S— or any mixture of R— and S—; 
 each R a  is independently selected from the group consisting of halogen; —(C 1 -C 8 )hydrocarbyl, —C(═O)R 2 , —NR 2   2 , —NHC(═O)R 3 , —NHSO 2 R 3 , —NHR 4 , —NHCR 2 R 4 C(═O)R 6 , —C(═O)OR 2 , —C(═O)NHR 2 ; —NO 2 , —CN, —OR 2 , —P(═O)(OH) 2 , dimethylamino(C 2 -C 6  alkoxy), —NHC(═NH)NHR 2 , —(C 1 -C 6 )haloalkyl, —(C 1 -C 6 )haloalkoxy and —N═CH—R 7 ; 
 each R b  attached to aryl is independently selected from the group consisting of —C(═O)R 2 , halogen, —NO 2 , —CN, —OR 2 , —C(═O)OR 2 , —NR 2   2 , (C 1 -C 6 )haloalkyl and (C 1 -C 6 )haloalkoxy; 
 each R b  attached to heteroaryl is independently selected from the group consisting of —(C 1 -C 8 )hydrocarbyl, —C(═O)R 2 , halogen, —NO 2 , —CN, —OR 2 , —C(═O)OR 2 , —NR 2   2 , (C 1 -C 6 )haloalkyl and (C 1 -C 6 )haloalkoxy; 
 each R 2  is independently selected from the group consisting of —H and —(C 1 -C 8 )hydrocarbyl; 
 each R 3  is independently selected from the group consisting of —H, —(C 1 -C 8 )hydrocarbyl, —O(C 1 -C 8 )hydrocarbyl, substituted and unsubstituted aryl, substituted heterocyclyl(C 1 -C 3 )alkyl, heteroaryl(C 1 -C 3 )alkyl, —(C 2 -C 10 )heteroalkyl, —(C 1 -C 6 )haloalkyl, —CR 2 R 4 NHR 5 , —N(R 2 ) 2 , —(C 1 -C 3 )alkyleneNH 2 , —(C 1 -C 3 )alkylene-N(CH 3 ) 2 , —(C 1 -C 3 )perfluoroalkylene-N(CH 3 ) 2 , —(C 1 -C 3 )alkylene-N + ((C 1 -C 3 )alkyl) 3 , —(C 1 -C 3 )alkylene-N + (CH 2 CH 2 OH) 3 , —(C 1 -C 3 )alkylene-OR 2 , —(C 1 -C 4 )alkylene-CO 2 R 2 , —(C 1 -C 4 )alkylene-C(═O)halogen, halo(C 1 -C 3 )alkyl-, —(C 1 -C 3 )alkylene-C(═O)(C 1 -C 3 )alkyl, and —(C 1 -C 4 )perfluoroalkylene-CO 2 R 2 ; 
 each R 4  is independently selected from the group consisting of —H, —(C 1 -C 6 )alkyl, —(CH 2 ) 3 —NH—C(NH 2 )(═NH), —CH 2 C(═O)NH 2 , —CH 2 COOH, —CH 2 SH, —(CH 2 ) 2 C(═O)—NH 2 , —(CH 2 ) 2 COOH, —CH 2 -(2-imidazolyl), —(CH 2 ) 4 —NH 2 , —(CH 2 ) 2 —S—CH 3 , phenyl, —CH 2 -phenyl, —CH 2 —OH, —CH(OH)—CH 3 , —CH 2 -(3-indolyl), and —CH 2 -(4-hydroxyphenyl); 
 each R 5  is independently selected from the group consisting of —H and a carboxy terminally linked peptidyl residue containing from 1 to 3 amino acids in which the terminal amino group of the peptidyl residue is present as a functional group selected from the group consisting of —NH 2  and —NHC(═O)(C 1 -C 6 )alkyl, —NH(C 1 -C 6 )alkyl, —N(C 1 -C 6 alkyl) 2  and —NHC(═O)O(C 1 -C 7 )hydrocarbyl; 
 each R 6  is independently selected from the group consisting of —OR 2  and an N-terminally linked peptidyl residue containing from 1 to 3 amino acids in which the terminal carboxyl group of the peptidyl residue is present as a functional group selected from the group consisting of —CO 2 R 2  and —C(═O)NR 2   2 ; and 
 each R 7  is independently selected from the group consisting of substituted and unsubstituted aryl and substituted and unsubstituted heteroaryl; 
 * indicates that, when R 1  is other than —H, the configuration of the substituents on the designated carbon atom is R—, S— or any mixture of R— and S—; or a salt of such a compound. 
 
     
     
       2. A compound according to  claim 1  of Formula IAz: 
       
         
           
           
               
               
           
         
       
       or a salt thereof. 
     
     
       3. A compound according to  claim 1  of the Formula IAe: 
       
         
           
           
               
               
           
         
       
       or a salt thereof. 
     
     
       4. A compound according to  claim 1 , or a salt thereof, wherein the sum of x and y is greater than zero. 
     
     
       5. A compound according to  claim 4 , or a salt thereof, wherein A 1  is an aryl radical. 
     
     
       6. A compound according to  claim 5  selected from the group consisting of: (1E)-2-(4-fluorophenyl)-1-[(naphthylmethyl)sulfinyl]ethene; (1E)-2-(4-chlorophenyl)-1-[(naphthylmethyl)sulfinyl]ethene; (1E)-2-(4-bromophenyl)-1-[(naphthylmethyl)sulfinyl]ethene; (1E)-2-(2-nitrophenyl)-1-[(naphthylmethyl)sulfinyl]-ethene; (1E)-2-(3-nitrophenyl)-1-[(naphthylmethyl)sulfinyl]ethene; and (1E)-2-(4-nitrophenyl)-1-[(naphthylmethyl)sulfinyl]ethene. 
     
     
       7. A compound according to  claim 5 , of Formula IB: 
       
         
           
           
               
               
           
         
       
       or a salt thereof. 
     
     
       8. A compound according to  claim 7 , or a salt thereof, wherein each R a  is independently selected from the group consisting of halogen, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, —NO 2 , —CN, —C(═O)OR 2 , —OH, —NH 2 , (C 1 -C 6 )trifluoroalkoxy and —CF 3 . 
     
     
       9. A compound according to  claim 7 , of Formula IC: 
       
         
           
           
               
               
           
         
       
       or a salt thereof. 
     
     
       10. A compound according to  claim 9  wherein each R a  is independently selected from the group consisting of halogen, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, —NO 2 , —CN and —CF 3 , and each R b  is independently selected from the group consisting of halogen, (C 1 -C 6 )alkoxy, —NO 2 , —CN and —CF 3 . 
     
     
       11. A compound according to  claim 9 , or a salt thereof, wherein the configuration of the substituents on the carbon-carbon double bond is E-. 
     
     
       12. A compound according to  claim 11 , or a salt thereof, wherein x is 0, 1 or 2and y is 1 or 2. 
     
     
       13. A compound according to  claim 11  selected from the group consisting of: (1E)-1-{[(3-amino-4-methoxyphenyl)methyl]sulfinyl}-2-(2,4,6-trimethoxyphenyl)ethene; (1E)-1-{[(3-hydroxy-4-methoxyphenyl)methyl]sulfinyl}-2-(2,4,6-trimethoxyphenyl)ethene; (1E)-1-{[(4-methoxy-3-nitrophenyl)methyl]sulfinyl}-2-(2,4,6-trimethoxyphenyl)ethene; 2-({[5-({[(1E)-2-(2,4,6-trimethoxyphenyl)vinyl]-sulfinyl}-methyl)-2-methoxyphenyl]amino}sulfonyl)acetic acid; 2-{N-[5-({[(1E)-2-(2,4,6-trimethoxyphenyl)vinyl]sulfinyl}-methyl)-2-methoxyphenyl]carbamoyl}acetic acid; [5-({[(1E)-2-(2,4,6-trimethoxyphenyl)vinyl]sulfinyl}methyl)-2-methoxyphenyl]aminocarboxamidine; 2-{[5-({[(1E)-2-(2,4,6-trimethoxyphenyl)vinyl]sulfinyl}methyl)-2-methoxyphenyl]amino}acetic acid; N-[5-({[(1E)-2-(2,4,6-trimethoxyphenyl)vinyl]sulfinyl}methyl)-2-methoxyphenyl](3,5-dinitro-phenyl)carboxamide; N-[5-({[(1E)-2-(2,4,6-trimethoxyphenyl)vinyl]sulfinyl}methyl)-2-methoxyphenyl](3,5-diaminophenyl)carboxamide; N-[5-({[(1E)-2-(2,4,6-trimethoxy-phenyl)vinyl]sulfinyl}methyl)-2-methoxyphenyl]-2-chloroacetamide; N-[5-({[(1E)-2-(2,4,6-trimethoxyphenyl)vinyl]sulfinyl}methyl)-2-methoxyphenyl]-2-(4-methyl-piperazinyl)acetamide; N-[5-({[(1E)-2-(2,4,6-trimethoxyphenyl)vinyl]sulfinyl}methyl)-2-methoxyphenyl]benzamide; N-[5-({[(1E)-2-(2,4,6-trimethoxyphenyl)vinyl]sulfinyl}-methyl)-2-methoxyphenyl](4-nitrophenyl)carboxamide; N-[5-({[(1E)-2-(2,4,6-trimethoxyphenyl)vinyl]sulfinyl}methyl)-2-methoxyphenyl](4-aminophenyl)carboxamide; N-[5-({[(1E)-2-(2,4,6-trimethoxyphenyl)-vinyl]sulfinyl}methyl)-2-methoxyphenyl](2R)-2,6-diaminohexanamide; N-[5-({[(1E)-2-(2,4,6-trimethoxyphenyl)vinyl]sulfinyl}methyl)-2-methoxyphenyl](2R)-2-amino-3-hydroxypropanamide; N-[5-({[(1E)-2-(2,4,6-trimethoxyphenyl)vinyl]sulfinyl}methyl)-2-methoxyphenyl](2S)-2-amino-3-hydroxypropanamide; N-[5-({[(1E)-2-(2,4,6-trimethoxyphenyl)vinyl]sulfinyl}methyl)-2-methoxyphenyl]aminamide; (1E)-1-({[4-methoxy-3-(methylamino)phenyl]methyl}sulfinyl)-2-(2,4,6-trimethoxyphenyl)ethene; N-[5-({[(1E)-2-(2,4,6-trimethoxyphenyl)vinyl]sulfinyl}methyl)-2-methoxyphenyl]acetamide; [5-({[(1E)-2-(2,4,6-trimethoxyphenyl)vinyl]sulfinyl}methyl)-2-methoxyphenyl][(2,4-dinitrophenyl)sulfonyl]amine; [5-({[(1E)-2-(2,4,6-trimethoxyphenyl)vinyl]sulfinyl}methyl)-2-methoxyphenyl][(2,4-diaminophenyl)sulfonyl]amine; N-[5-({[(1E)-2-(2,4,6-trimethoxyphenyl)vinyl]sulfinyl}methyl)-2-methoxyphenyl]-2-(dimethylamino)-acetamide; 2-{[5-({[(1E)-2-(2,4,6-trimethoxyphenyl)vinyl]sulfinyl}methyl)-2-methoxy-phenyl]amino}propanoic acid; N-[5-({[(1E)-2-(2,4,6-trimethoxyphenyl)vinyl]sulfinyl}-methyl)-2-methoxyphenyl][4-(4-methylpiperazinyl)phenyl]carboxamide; N-[5-({[(1E)-2-(2,4,6-trimethoxyphenyl)vinyl]sulfinyl}methyl)-2-methoxyphenyl]-2-hydroxyacetamide; N-[5-({[(1E)-2-(2,4,6-trimethoxyphenyl)vinyl]sulfinyl}methyl)-2-methoxyphenyl]-2-pyridylacetamide; {N-[5-({[(1E)-2-(2,4,6-trimethoxyphenyl)vinyl]sulfinyl}methyl)-2-methoxyphenyl]carbamoyl}methyl acetate; N-[5-({[(1E)-2-(2,4,6-trimethoxy-phenyl)vinyl]sulfinyl}methyl)-2-methoxyphenyl]-2-hydroxypropanamide; N-[5-({[(1E)-2-(2,4,6-trimethoxyphenyl)vinyl]sulfinyl}methyl)-2-methoxyphenyl]-2-(triethylamino)acetamide; N-[5-({[(1E)-2-(2,4,6-trimethoxyphenyl)vinyl]sulfinyl}-methyl)-2-methoxyphenyl]-2-[tris(2-hydroxyethyl)amino]acetamide; N-[5-({[(1E)-2-(2,4,6-trimethoxyphenyl)vinyl]sulfinyl}methyl)-2-methoxyphenyl]-2-hydroxy-2-methylpropanamide; 1-{N-[5-({[(1E)-2-(2,4,6-trimethoxyphenyl)vinyl]sulfinyl}-methyl)-2-methoxyphenyl]carbamoyl}-isopropyl acetate; N-[5-({[(1E)-2-(2,4,6-trimethoxyphenyl)vinyl]sulfinyl}methyl)-2-methoxyphenyl]-2,2,2-trifluoroacetamide; [5-({[(1E)-2-(2,4,6-trimethoxyphenyl)vinyl]sulfinyl}methyl)-2-methoxyphenyl][(trifluoro-methyl)sulfonyl]amine; 3-{N-[5-({[(1E)-2-(2,4,6-trimethoxyphenyl)vinyl]-sulfinyl}methyl)-2-methoxyphenyl]carbamoyl}propanoic acid; 3-{N-[5-({[(1E)-2-(2,4,6-trimethoxyphenyl)vinyl]sulfinyl}-methyl)-2-methoxyphenyl]carbamoyl}propanoyl chloride; 3-[({N-[5-({[(1E)-2-(2,4,6-trimethoxyphenyl)vinyl]sulfinyl}-methyl)-2-methoxyphenyl]carbamoyl}methyl)oxycarbonyl]propanoic acid; 4-{N-[5-({[(1E)-2-(2,4,6-trimethoxyphenyl)vinyl]sulfinyl}-methyl)-2-methoxyphenyl]carbamoyl}butanoic acid; N-[5-({[(1E)-2-(2,4,6-trimethoxyphenyl)vinyl]sulfinyl}methyl)-2-methoxyphenyl]-2-(phosphonooxy)acetamide, disodium salt; 4-{[5-({[(1E)-2-(2,4,6-trimethoxy-phenyl)vinyl]sulfinyl}methyl)-2-methoxyphenyl]amino}butanoic acid; 3-{[5-({[(1E)-2-(2,4,6-trimethoxyphenyl)vinyl]sulfinyl}methyl)-2-methoxyphenyl]amino}propanoic acid; N-[5-({[(1E)-2-(2,4,6-trimethoxyphenyl)vinyl]sulfinyl}methyl)-2-methoxyphenyl]methoxycarboxamide; [5-({[(1E)-2-(2,4,6-trimethoxy-phenyl)vinyl]sulfinyl}methyl)-2-methoxyphenyl][(4-methoxyphenyl)sulfonyl]amine; {N-[5-({[(1E)-2-(2,4,6-trimethoxyphenyl)vinyl]sulfinyl}methyl)-2-methoxyphenyl]carbamoyl}ethyl acetate; methyl-3-{N-[5-({[(1E)-2-(2,4,6-trimethoxyphenyl)vinyl]-sulfinyl}-methyl)-2-methoxyphenyl]carbamoyl}propanoate; ethyl-2-{N-[5-({[(1E)-2-(2,4,6-trimethoxyphenyl)vinyl]sulfinyl}-methyl)-2-methoxyphenyl]carbamoyl}acetate; N-[5-({[(1E)-2-(2,4,6-trimethoxy-phenyl)vinyl]sulfinyl}methyl)-2-methoxyphenyl]-2,2,3,3,3-pentafluoropropanamide; methyl-2-{N-[5-({[(1E)-2-(2,4,6-trimethoxyphenyl)vinyl]-sulfinyl}methyl)-2-methoxy-phenyl]carbamoyl}-2,2-difluoroacetate; 3-{N-[5-({[(1E)-2-(2,4,6-trimethoxyphenyl)vinyl]sulfinyl}-methyl)-2-methoxyphenyl]carbamoyl}-2,2,3,3-tetrafluoropropanoic acid; N-[5-({[(1E)-2-(2,4,6-trimethoxy-phenyl)vinyl]sulfinyl}methyl)-2-methoxyphenyl]-2-aminoacetamide; 2-{N-[5-({[(1E)-2-(2,4,6-trimethoxyphenyl)vinyl]sulfinyl}-methyl)-2-methoxyphenyl]carbamoyl}-2,2-difluoroacetic acid; N-[5-({[(1E)-2-(2,4,6-trimethoxyphenyl)vinyl]sulfinyl}methyl)-2-methoxyphenyl]-2-(dimethylamino)-2,2-difluoroacetamide, 4-((1E)-2-{[(4-fluorophenyl)methyl]sulfinyl}vinyl)benzoic acid; 4-((1E)-2-{[(4-iodophenyl)methyl]-sulfinyl}vinyl)benzoic acid; 4-((1E)-2-{[(4-chlorophenyl)methyl]sulfinyl}vinyl)benzoic acid; 1-[5-((1E)-2-{[(4-chlorophenyl)methyl]sulfinyl}vinyl)-2-fluoro-phenyl]-2-(dimethylamino)ethan-1-one; (1E)-2-(2,4-difluorophenyl)-1-{[(4-bromophenyl)methyl]-sulfinyl}ethene; (1E)-2-(3-amino-4-fluorophenyl)-1-{[(4-chlorophenyl)methyl]sulfinyl}-ethene; (1E)-1-{[(4-fluorophenyl)methyl]sulfinyl}-2-(2,3 ,4,5,6-pentafluorophenyl)-ethene; (1E)-1-{[(4-chlorophenyl)methyl]sulfinyl}-2-(2,3,4,5,6-pentafluoro-phenyl)ethene; (1E)-1-{[(4-bromophenyl)methyl]sulfinyl}-2-(2,3,4,5,6-pentafluoro-phenyl)ethene; (1E)-2-(4-fluorophenyl)-1-{[(2,3,4,5,6-pentafluorophenyl)-methyl]sulfinyl}ethene; (1E)-2-(4-chlorophenyl)-1-{[(2,3,4,5,6-pentafluorophenyl)-methyl]sulfinyl}ethene; (1E)-2-(4-bromophenyl)-1-{[(2,3,4,5,6-pentafluorophenyl)-methyl]sulfinyl}ethene; (1E)-1-{[(3,4-dichlorophenyl)methyl]sulfinyl}-2-(2,3,4,5,6-pentafluorophenyl)ethene; (1E)-1-{[(4-iodophenyl)methyl]sulfinyl}-2-(2,3,4,5,6-pentafluorophenyl)ethene; (1E) 1-{[(4-fluorophenyl)methyl]sulfinyl}-2-(2-hydroxy-3,5-dinitrophenyl)ethene; (1E)-1-{[(4-bromophenyl)methyl]sulfinyl}-2-(2-hydroxy-3,5-dinitrophenyl)ethene; (1E)-1-{[(4-chlorophenyl)methyl]sulfinyl}-2-(2-hydroxy-3,5-dinitrophenyl)ethene; (1E)-1-{[(2,4-dichlorophenyl)methyl]sulfinyl}-2-(2-hydroxy-3,5-dinitrophenyl)ethene; (1E)-1-{[(4-methoxyphenyl)methyl]sulfinyl}-2-(2,4,6-trimethoxy-phenyl)ethene; (1E)-1-{[(4-methoxyphenyl)methyl]sulfinyl}-2-(3,4,5-trimethoxy-phenyl)ethene; (1E)-1-{[(2-nitro-4,5-dimethoxyphenyl)methyl]sulfinyl}-2-(3,4,5-trimethoxyphenyl)ethene; (1E)-1-{[(2-nitro-4,5-dimethoxyphenyl)methyl]sulfinyl}-2-(2,4,6-trimethoxyphenyl)ethene; (1E)-1-{[(4-fluorophenyl)methyl]sulfinyl}-2-(2,3,4-trifluorophenyl)ethene; (1E)-1-{[(4-chlorophenyl)methyl]sulfinyl}-2-(2,3,4-trifluorophenyl)ethene; (1E)-1-{[(4-methoxyphenyl)methyl]sulfinyl}-2-(2,6-methoxy-4-hydroxyphenyl)ethene; (1E)-1-{[(4-methoxyphenyl)methyl]sulfinyl}-2-(2,3,5,6-tetrafluorophenyl)ethene; (1E)-1-{[(4-methoxyphenyl)methyl]sulfinyl}-2-(2,4,5-trimethoxyphenyl)ethene; (1E)-1-{[(4-methoxyphenyl)methyl]sulfinyl}-2-(2,3,4-trimethoxyphenyl)ethene; (1E)-1-{[(4-methoxyphenyl)methyl]sulfinyl}-2-(3-nitro-4-hydroxy-5-methoxyphenyl)ethene; (1E)-1-{[(4-methoxyphenyl)methyl]sulfinyl}-2-(3,4-dimethoxy-6-nitrophenyl)ethene; (1E)-1-{[(4-methoxyphenyl)methyl]sulfinyl}-2-(3,4-dimethoxy-5-iodophenyl)ethene; (1E)-1-{[(4-methoxyphenyl)methyl]sulfinyl}-2-(2,6-dimethoxy-4-fluorophenyl)ethene; (1E)-1-{[(4-methoxyphenyl)methyl]sulfinyl}-2-(2-hydroxy-4,6-dimethoxyphenyl)ethene; (1E)-1-{[(4-chlorophenyl)methyl]sulfinyl}-2-(2,4,6-trimethoxyphenyl)ethene; (1E)-1-{[(4-chlorophenyl)methyl]sulfinyl}-2-(2,6-dimethoxy-4-fluorophenyl)ethene; (1E)-1-{[(4-chlorophenyl)methyl]sulfinyl}-2-(2-hydroxy-4,6-dimethoxyphenyl)ethene; (1E)-1-{[(4-bromophenyl)methyl]sulfinyl}-2-(2,4,6-trimethoxyphenyl)ethene; (1E)-1-{[(4-bromophenyl)methyl]sulfinyl}-2-(2,6-dimethoxy-4-fluorophenyl)ethene; (1E)-1-{[(2,4,6-trimethoxyphenyl)methyl]sulfinyl}-2-(2,4,6-trimethoxyphenyl)ethene; (1E)-1-{[(2,3,4-trimethoxyphenyl)methyl]sulfinyl}-2-(2,6-dimethoxyphenyl)ethene; (1E)-1-{[(3,4,5-trimethoxyphenyl)methyl]sulfinyl}-2-(2,4,6-trimethoxyphenyl)ethene; (1E)-1-{[(3,4,5-trimethoxyphenyl)methyl]sulfinyl}-2-(2,6-dimethoxyphenyl)ethene; (1E)-1-{[(3,4,5-trimethoxyphenyl)methyl]sulfinyl}-2-(4-fluorophenyl)ethene; (1E)-2-(4-fluorophenyl)-1-({[4-(trifluoromethyl)phenyl]methyl}-sulfinyl)ethene; (1E)-2-(4-chlorophenyl)-1-({[4-(trifluoromethyl)phenyl]methyl}-sulfinyl)ethene; (1E)-2-(4-bromophenyl)-1-({[4-(trifluoromethyl)phenyl]methyl}-sulfinyl)ethene; (1E)-1-{[(2,4-dichlorophenyl)methyl]sulfinyl}-2-(4-fluorophenyl)ethene; (1E)-1-{[(2,4-dichlorophenyl)methyl]sulfinyl}-2-(4-chloro-phenyl)ethene; (1E)-1-{[(3,4-dichlorophenyl)methyl]sulfinyl}-2-(4-fluoro-phenyl)ethene; (1E)-1-{[(3,4-dichloro-phenyl)methyl]sulfinyl}-2-(4-chloro-phenyl)ethene; (1E)-1-{[(3,4-dichloro-phenyl)methyl]sulfinyl}-2-(4-bromo-phenyl)ethene; (1E)-2-(4-fluorophenyl)-1-{[(4-nitrophenyl)methyl]sulfinyl}-ethene; 4-({[(1E)-2-(4-fluorophenyl)vinyl]-sulfinyl }methyl)benzene-carbonitrile; 4-({[(1E)-2-(4-chlorophenyl)vinyl]sulfinyl}-methyl)benzene-carbonitrile; 4-({[(1E)-2-(4-bromophenyl)vinyl]sulfinyl}-methyl)benzene-carbonitrile; (1E)-2-(3,4-difluorophenyl)-1-{[(4-chlorophenyl)methyl]-sulfinyl}ethene; (1E)-2-(3-chloro-4-fluorophenyl)-1-{[(4-chlorophenyl)methyl]-sulfinyl}ethene; (1E)-2-(2-chloro-4-fluorophenyl)-1-{[(4-chlorophenyl)methyl]-sulfinyl}ethene; (1E)-2-(2,4-dichlorophenyl)-1-{[(4-chlorophenyl)methyl]-sulfinyl}ethene; (1E)-2-(3,4-dichlorophenyl)-1-{[(4-chlorophenyl)-methyl]sulfinyl}ethene; (1E)-2-(2,3-dichlorophenyl)-1-{[(4-chlorophenyl)methyl]-sulfinyl}ethene; (1E)-2-(4-fluorophenyl)-1-{[(4-iodophenyl)methyl]-sulfinyl}ethene; (1E)-1-{[(4-fluorophenyl)methyl]sulfinyl}-2-(4-iodophenyl)-ethene; (1E)-1-{[(4-chlorophenyl)methyl]sulfinyl}-2-(4-iodophenyl)-ethene; (1E)-1-{[(4-bromophenyl)methyl]sulfinyl}-2-(4-iodophenyl)-ethene; (1E)-1-{[(4-bromophenyl)methyl]sulfinyl}-2-(4-chlorophenyl)-ethene; (1E)-2-(4-bromophenyl)-1-{[(4-iodophenyl)methyl]sulfinyl}ethene; (1E)-1-{[(4-iodophenyl)methyl]sulfinyl}-2-(4-nitrophenyl)-ethene; (1E)-1-{[(4-iodophenyl)methyl]sulfinyl}-2-(2-nitrophenyl)-ethene; (1E)-2-(4-iodophenyl)-1-{[(4-methoxyphenyl)methyl]sulfinyl}-ethene; (1E)-1-{[(2,4-dichlorophenyl)methyl]sulfinyl}-2-(4-iodophenyl)-ethene; (1E)-2-(3,4-dichlorophenyl)-1-{[(4-chlorophenyl)methyl]-sulfinyl}ethene; (1E)-2-(2-nitrophenyl)-1-{[(4-fluoro-phenyl)methyl]sulfinyl}-ethene; (1E)-2-(3-nitrophenyl)-1-{[(4-fluorophenyl)methyl]-sulfinyl}-ethene; (1E)-2-(4-nitrophenyl)-1-{[(4-fluorophenyl)methyl]sulfinyl}-ethene; (1E)-2-(2-trifluoromethylphenyl)-1-{[(4-fluorophenyl)methyl]sulfinyl}ethene; (1E)-2-(3-trifluoromethylphenyl)-1-{[(4-fluorophenyl)methyl]-sulfinyl}ethene; (1E)-2-(4-trifluoromethylphenyl)-1-{[(4-fluorophenyl)methyl]-sulfinyl}ethene; (1E)-2-(2-trifluoro-methyl-4-fluorophenyl)-1-{[(4-fluorophenyl)-methyl]sulfinyl}ethene; (1E)-2-(2-nitrophenyl)-1-{[(4-chlorophenyl)methyl]sulfinyl}-ethene; (1E)-2-(3-nitrophenyl)-1-{[(4-chlorophenyl)methyl]sulfinyl}-ethene; (1E)-2-(4-nitrophenyl)-1-{[(4-chlorophenyl)-methyl]sulfinyl}-ethene; (1E)-2-(2-trifluoromethylphenyl)-1-{[(4-chlorophenyl)methyl]-sulfinyl}ethene; (1E)-2-(3-trifluoromethylphenyl)-1-{[(4-chlorophenyl)methyl]-sulfinyl}ethene; (1E)-2-(4-trifluoromethylphenyl)-1-{[(4-chlorophenyl)-methyl]sulfinyl}ethene; (1E)-2-(2-trifluoromethyl-4-fluorophenyl)-1-{[(4-chlorophenyl)-methyl]sulfinyl}ethene; (1E)-2-(2-nitrophenyl)-1-{[(2,4-dichlorophenyl)methyl]sulfinyl}-ethene; (1E)-2-(2-trifluoromethyl-4-fluorophenyl)-1-{[(2,4-dichloro-phenyl)methyl]sulfinyl}ethene; (1E)-2-(2-nitrophenyl)-1-{[(4-bromophenyl)methyl]sulfinyl}ethene; (1E)-2-(3-nitrophenyl)-1-{[(4-bromophenyl)methyl]sulfinyl}ethene; (1E)-2-(4-nitrophenyl)-1-{[(4-bromophenyl)methyl]sulfinyl}ethene; (1E)-2-(2-trifluoromethylphenyl)-1-{[(4-bromophenyl)methyl]sulfinyl}ethene; (1E)-2-(3-trifluoromethylphenyl)-1-{[(4-fluorophenyl)methyl]sulfinyl}ethene; (1E)-2-(4-trifluoromethylphenyl)-1-{[(4-bromophenyl)methyl]sulfinyl}ethene; (1E)-2-(2-nitrophenyl)-1-{[(4-cyanophenyl)methyl]sulfinyl}ethene; (1E)-2-(3-nitrophenyl)-1-{[(4-cyanophenyl)-methyl]sulfinyl}ethene; (1E)-2-(4-nitrophenyl)-1-{[(4-cyanophenyl)-methyl]sulfinyl}ethene; (1E)-2-(4-fluorophenyl)-1-{[(4-methylphenyl)methyl]sulfinyl}-ethene; (1E)-2-(4-bromophenyl)-1-{[(4-methylphenyl)methyl]sulfinyl}ethene; (1E)-2-(2-nitrophenyl)-1-{[(4-methylphenyl)methyl]sulfinyl}ethene; (1E)-2-(3-nitrophenyl)-1-{[(4-methylphenyl)methyl]sulfinyl}ethene; (1E)-2-(4-nitrophenyl)-1-{[(4-methylphenyl)methyl]sulfinyl}ethene; (1E)-2-(4-fluorophenyl)-1-{[(4-methoxyphenyl)methyl]sulfinyl}ethene; (1E)-2-(4-chlorophenyl)-1-{[(4-methoxyphenyl)methyl]-sulfinyl}ethene; (1E)-2-(4-bromophenyl)-1-{[(4-methoxyphenyl)methyl]-sulfinyl}ethene; (1E)-2-(2-nitrophenyl)-1-{[(4-methoxyphenyl)methyl]sulfinyl}ethene; (1E)-2-(3-nitrophenyl)-1-{[(4-methoxyphenyl)methyl]sulfinyl}ethene; (1E)-2-(4-nitrophenyl)-1-{[(4-methoxy-phenyl)methyl]sulfinyl}ethene; (1E)-2-(4-chlorophenyl)-1-{[(4-nitrophenyl)methyl]-sulfinyl}ethene; (1E)-2-(4-fluorophenyl)-1-{[(4-nitrophenyl)methyl]sulfinyl}ethene; and salts thereof. 
     
     
       14. A compound according to  claim 9  wherein:
 R a  is selected from the group consisting of chlorine, fluorine and bromine, and said R a  is bonded to the para position of the ring to which it is attached; 
 x is 0 or 1; 
 R b  is selected from the group consisting of chlorine, fluorine, bromine, and methoxy, and said R b  is bonded to the ortho or para position of the ring to which it is bonded; and 
 y is 1, 2 or 3. 
 
     
     
       15. A compound according to  claim 14  wherein the configuration of the substituents on the carbon-carbon double bond is E-. 
     
     
       16. A compound according to  claim 15  selected from the group consisting of: (1E)-2-(2-chlorophenyl)-1-[benzylsulfinyl]ethene; (1E)-2-(4-chlorophenyl)-1-[benzylsulfinyl]ethene; (1E)-1-{[(4-chlorophenyl)methyl]sulfinyl}-2-(4-fluorophenyl)ethene; (1E)-2-(4-chlorophenyl)-1-{[(4-chlorophenyl)methyl]sulfinyl}-ethene; (1E)-2-(4-fluorophenyl)-1-{[(4-fluorophenyl)methyl]sulfinyl}ethene; (1E)-2-(2,4-difluorophenyl)-1-{[(4-fluorophenyl)methyl]sulfinyl}ethene; (1E)-1-{[(4-bromophenyl)methyl]sulfinyl}-2-(4-fluorophenyl)ethene; (1E)-2-(4-bromophenyl)-1-{[(4-bromophenyl)methyl]sulfinyl}ethene; (1E)-2-(4-bromophenyl)-1-{[(4-fluorophenyl)methyl]sulfinyl}ethene; and (1E)-1-{[(4-bromophenyl)methyl]sulfinyl}-2-(4-chlorophenyl)ethene. 
     
     
       17. A compound according to  claim 9 , wherein:
 each R a  is independently selected from the group consisting of halogen, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, —NO 2 , —CN and —CF 3 , and each R b  is independently selected from the group consisting of (C 1 -C 6 )alkoxy, halogen and nitro, and is bonded to the ortho or para position of the ring to which it is attached; 
 x is 0, 1, 2 or 3; and 
 y is 1, 2 or 3. 
 
     
     
       18. A compound according to  claim 17 , wherein the configuration of the substituents on the carbon-carbon double bond is Z—. 
     
     
       19. A compound according to  claim 18  selected from the group consisting of: (1Z)-2-(4-chlorophenyl)-1-[benzylsulfinyl]ethene; (1Z)-2-(4-chlorophenyl)-1-{[(4-chlorophenyl)methyl]sulfinyl}-ethene; (1Z)-2-(4-chlorophenyl)-1-{[(2-chlorophenyl)methyl]sulfinyl}-ethene; (1Z)-2-(4-chlorophenyl)-1-{[(4-fluorophenyl)methyl]sulfinyl}ethene; (1Z)-2-(4-fluorophenyl)-1-[benzylsulfinyl]ethene; (1Z)-2-(4-fluorophenyl)-1-{[(4-chlorophenyl)methyl]sulfinyl}ethene; (1Z)-2-(4-fluoro-phenyl)-1-{[(2-chlorophenyl)methyl]sulfinyl}ethene; (1Z)-2-(4-fluorophenyl)-1-{[(4-fluorophenyl)methyl]sulfinyl}ethene; (1Z)-2-(4-bromophenyl)-1-[benzylsulfinyl]ethene; (1Z)-2-(4-bromophenyl)-1-{[(4-chlorophenyl)methyl]sulfinyl}ethene; (1Z)-2-(4-bromophenyl)-1-{[(2-chlorophenyl)methyl]sulfinyl}ethene; (1Z)-2-(4-bromophenyl)-1-{[(4-fluorophenyl)methyl]sulfinyl}ethene; and (1Z)-2-(4-fluorophenyl)-1-{[(4-iodophenyl)methyl]sulfinyl}ethene. 
     
     
       20. A compound according to  claim 4 , of Formula ID: 
       
         
           
           
               
               
           
         
         wherein B 2  is selected from the group consisting of heteroaryl and aryl other than phenyl 
         or a salt thereof. 
       
     
     
       21. A compound according to  claim 20 , or a salt thereof, wherein B 2  is heteroaryl. 
     
     
       22. A compound according to  claim 20 , or a salt thereof, wherein B 2  is selected from the group consisting of furyl, thienyl, pyrrolyl, thiazolyl, pyridyl, thienyl-1,1-dioxide, anthryl, and naphthyl. 
     
     
       23. A compound according to  claim 22 , or a salt thereof, wherein the configuration of the substituents on the carbon-carbon double bond is E-. 
     
     
       24. A compound according to  claim 23 , or a salt thereof, wherein R a  is independently selected from the group consisting of halogen, (C 1 -C 3 )alkoxy, —CN, —NO 2 , and —CF 3 . 
     
     
       25. A compound of  claim 24  selected from the group consisting of: (1E)-1-{[(4-fluorophenyl)methyl]sulfinyl}-2-(2-pyridyl)ethene; (1E)-1-{[(4-fluorophenyl)methyl]-sulfinyl}-2-(3-pyridyl)ethene; (1E)-1-{[(4-fluorophenyl)methyl]sulfinyl}-2-(4-pyridyl)ethene; (1E)-1-{[(4-chlorophenyl)methyl]sulfinyl}-2-(2-pyridyl)ethene; (1E)-1-{[(4-chlorophenyl)methyl]sulfinyl}-2-(3-pyridyl)ethene; (1E)-1-{[(4-chlorophenyl)methyl]sulfinyl}-2-(4-pyridyl)ethene; (1E)-1-{[(4-bromophenyl)methyl]sulfinyl}-2-(2-pyridyl)ethene; (1E)-1-{[(4-bromophenyl)methyl]-sulfinyl}-2-(3-pyridyl)ethene; (1E)-1-{[(4-bromophenyl)methyl]sulfinyl}-2-(4-pyridyl)ethene; (1E)-1-{[(4-fluorophenyl)methyl]sulfinyl}-2-(2-thienyl)ethene; (1E)-1-{[(4-chlorophenyl)methyl]sulfinyl}-2-(2-thienyl)ethene; (1E)-1-{[(4-bromophenyl)methyl]sulfinyl}-2-(2-thienyl)ethene; (1E)-2-(4-bromo(2-thienyl))-1-{[(4-fluorophenyl)methyl]-sulfinyl}ethene; (1E)-2-(5-bromo(2-thienyl))-1-{[(4-fluorophenyl)methyl]-sulfinyl}ethene; (1E)-2-(5-bromo(2-thienyl))-1-{[(4-chlorophenyl)methyl]-sulfinyl}ethene; (1E)-2-(5-bromo(2-thienyl))-1-{[(4-bromophenyl)methyl]-sulfinyl}ethene; 2-((1E)-2-{[(4-fluorophenyl)methyl]sulfinyl}vinyl)thiole-1,1-dione; 2-((1E)-2-{[(4-chlorophenyl)-methyl]sulfinyl}vinyl)thiole-1,1-dione; 2-((1E)-2-{[(4-bromophenyl)methyl]-sulfinyl}vinyl)thiole-1,1-dione; (1E)-1-{[(4-fluorophenyl)methyl]sulfinyl}-2-(3-thienyl)ethene; (1E)-1-{[(4-chlorophenyl)methyl]sulfinyl}-2-(3-thienyl)ethene; (1E)-1-{[(4-bromophenyl)methyl]sulfinyl}-2-(3-thienyl)ethene; (1E)-1-{[(4-iodophenyl)methyl]sulfinyl}-2-(3-thienyl)ethene; (1E)-1-{[(4-methylphenyl)methyl]sulfinyl}-2-(3-thienyl)ethene; (1E)-1-{[(4-methoxyphenyl)-methyl]sulfinyl}-2-(3-thienyl)ethene; (1E)-1-{[(4-trifluoromethylphenyl)methyl]-sulfinyl}-2-(3-thienyl)-ethene; (1E)-1-{[(2,4-dichlorophenyl)methyl]sulfinyl}-2-(3-thienyl)-ethene; (1E)-1-{[(3,4-dichlorophenyl)methyl]sulfinyl}-2-(3-thienyl)-ethene; (1E)-1-{[(4-cyanophenyl)methyl]sulfinyl}-2-(3-thienyl)ethene; (1E)-1-{[(4-nitrophenyl)methyl]sulfinyl}-2-(3-thienyl)ethene; 3-((1E)-2-{[(4-fluorophenyl)methyl]sulfinyl}vinyl)thiole-1,1-dione; 3-((1E)-2-{[(4-chlorophenyl)methyl]sulfinyl}vinyl)thiole-1,1-dione; 3-((1E)-2-{[(4-bromophenyl)-methyl]sulfinyl}vinyl)thiole-1,1-dione; 3-((1E)-2-{[(4-methoxyphenyl)-methyl]sulfinyl}vinyl)thiole-1,1-dione; 3-((1E)-2-{[(2,4-dichlorophenyl)methyl]-sulfinyl}vinyl)thiole-1,1-dione; (1E)-1-{[(4-fluorophenyl)methyl]sulfinyl}-2-(2-furyl)ethene; (1E)-1-{[(4-chlorophenyl)methyl]sulfinyl}-2-(2-furyl)ethene; (1E)-1-{[(4-bromophenyl)methyl]sulfinyl}-2-(2-furyl)ethene; (1E)-1-{[(4-fluorophenyl)methyl]sulfinyl}-2-(3-furyl)ethene; (1E)-1-{[(4-chlorophenyl)-methyl]sulfinyl}-2-(3-furyl)ethene; (1E)-1-{[(4-bromophenyl)methyl]sulfinyl}-2-(3-furyl)ethene; (1E)-1-{[(4-iodophenyl)methyl]sulfinyl}-2-(3-furyl)ethene; (1E)-1-{[(4-methylphenyl)methyl]sulfinyl}-2-(3-furyl)ethene; (1E)-1-{[(4-methoxyphenyl)methyl]sulfinyl}-2-(3-furyl)ethene; (1E)-1-{[(4-trifluoromethylphenyl)methyl]sulfinyl}-2-(3-furyl)-ethene; (1E)-1-{[(2,4-dichlorophenyl)methyl]sulfinyl}-2-(3-furyl)ethene; (1E)-1-{[(3,4-dichlorophenyl)-methyl]sulfinyl}-2-(3-furyl)ethene; (1E)-1-{[(4-cyanophenyl)methyl]sulfinyl}-2-(3-furyl)ethene; (1E)-1-{[(4-nitrophenyl)methyl]sulfinyl}-2-(3-furyl)ethene; (1E)-1-{[(4-chlorophenyl)methyl]sulfinyl}-2-(1,3-thiazol-2-yl)-ethene; (1E)-1-{[(4-chlorophenyl)methyl]sulfinyl}-2-pyrrol-2-ylethene; (1E)-1-{[(4-bromophenyl)methyl]sulfinyl}-2-pyrrol-2-ylethene; (1E)-1-{[(4-chlorophenyl)-methyl]sulfinyl}-2-(5-nitro(3-thienyl))ethene; (1E)-1-{[(4-iodophenyl)methyl]sulfinyl}-2-(5-nitro(3-thienyl))ethene; (1E)-1-{[(2,4-dichlorophenyl)methyl]sulfinyl}-2-(5-nitro(3-thienyl))ethene; (1E)-1-{[(4-methoxyphenyl)methyl]sulfinyl}-2-(5-nitro(3-thienyl))ethene; (1E)-1-{[(4-fluorophenyl)methyl]sulfinyl}-2-naphthylethene; (1E)-1-{[(4-fluorophenyl)methyl]sulfinyl}-2-(2-naphthyl)ethene; (1E)-1-{[(4-chlorophenyl)methyl]sulfinyl}-2-naphthylethene; (1E)-1-{[(4-chlorophenyl)methyl]sulfinyl}-2-(2-naphthyl)ethene; (1E)-1-{[(4-bromophenyl)methyl]sulfinyl}-2-naphthylethene; (1E)-1-{[(4-bromophenyl)methyl]-sulfinyl}-2-(2-naphthyl)ethene; (1E)-2-(9-anthryl)-1-{[(4-fluorophenyl)-methyl ]sulfinyl}ethene; (1E)-2-(9-anthryl)-1-{[(4-chlorophenyl)methyl]sulfinyl}ethene; (1E)-2-(9-anthryl)-1-{[(4-bromophenyl)methyl]sulfinyl}ethene; and salts thereof. 
     
     
       26. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound according to  claim 1  or a pharmaceutically acceptable salt thereof. 
     
     
       27. A conjugate of the Formula, IC-L-Ab;
 wherein:
 IC is a compound according to  claim 9  or a pharmaceutically acceptable salt thereof; 
 Ab is an antibody; and 
 -L- is a single covalent bond or a linking group covalently linking said compound to said antibody. 
 
 
     
     
       28. A conjugate according to  claim 27  wherein said antibody Ab is a monoclonal antibody or a monospecific polyclonal antibody. 
     
     
       29. A conjugate according to  claim 28  wherein said antibody Ab is a tumor-specific antibody. 
     
     
       30. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and at least one conjugate according to  claim 27 . 
     
     
       31. A method of treating an individual for breast cancer, prostate cancer, lung cancer or colorectal cancer comprising administering to said individual in need of such treatment an effective amount of a compound according to  claim 9 , or a pharmaceutically acceptable salt thereof. 
     
     
       32. A method of treating an individual for a cancer selected from the group consisting of breast, prostate, lung, and colorectal cancers, comprising administering to said individual an effective amount of a compound according to claim  9 , or a pharmaceutically acceptable salt thereof, and administering an effective amount of therapeutic ionizing radiation to the individual. 
     
     
       33. A method of inducing apoptosis of tumor cells in an individual afflicted with breast cancer, prostate cancer, lung cancer or colorectal cancer comprising administering to said individual an effective amount of a compound according to  claim 9 , or a pharmaceutically acceptable salt thereof. 
     
     
       34. A method of treating an individual afflicted with breast cancer, prostate cancer, lung cancer or colorectal cancer, comprising administering to said individual an effective amount of at least one conjugate according to  claim 27 . 
     
     
       35. A process for preparing a compound according to  claim 3  comprising:
 (a) reacting a compound of Formula II′: 
 
       
         
           
           
               
               
           
         
         wherein A 1 , n, R 1 , R a  and x are defined as in  claim 1   
         with a compound of Formula III′: 
       
       
         
           
           
               
               
           
         
         wherein B 1 , R b  and y are defined as in  claim 1 ; and 
         (b) isolating a compound of  claim 3  from the reaction products. 
       
     
     
       36. A process according to  claim 35  wherein the compound of Formula II′ is prepared by:
 (a) reacting a compound of Formula IIA′: 
 
       
         
           
           
               
               
           
         
         with an oxidizing agent capable of oxidizing a sulfide to a sulfoxide; and 
         (b) isolating a compound of Formula II′ from the reaction products. 
       
     
     
       37. A process according to  claim 36  wherein the compound of Formula IIA′ 0  is prepared by:
 (a) reacting a compound of Formula IIB′: 
 
       
         
           
           
               
               
           
         
         wherein:
 L is a leaving group; 
 with mercaptoacetic acid; and 
 
         (b) isolating a compound of Formula IIA′ from the reaction products. 
       
     
     
       38. A process for preparing a compound according to  claim 2  comprising:
 (a) reacting a compound of Formula IV′: 
 
       
         
           
           
               
               
           
         
         wherein A 1 , B 1 , n, R 1 , R a , R b , x and y are defined as in  claim 1 ; 
         with an oxidizing agent capable of oxidizing a sulfide to a sulfoxide; and 
         (b) isolating a compound of  claim 2  from the reaction products. 
       
     
     
       39. A process according to  claim 38  wherein the compound of Formula IV′ is prepared by:
 (a) reacting a compound of Formula IVA′: 
 
       
         
           
           
               
               
           
         
         wherein Q +  is a counterion selected from the group consisting of alkali metals, alkaline earth metals and transition metals; 
         with a compound of Formula IVB′: 
       
       
         
           
           
               
               
           
         
         (b) isolating a compound of Formula IV′ from the reaction products. 
       
     
     
       40. An isolated optical isomer of a compound according to  claim 1 , or a salt thereof.